1. Field of Invention
The present invention is directed to the sterilization of liquid and gel or gel-like compositions that are useful as biomedical adhesives and sealants and particularly to sterilization of kits of such liquid and gel or gel-like compositions. In particular, the present invention relates to the application of separate sterilization processes to discrete components of the liquid and gel or gel-like compositions, and kits containing the liquid and gel or gel-like compositions assembled from components treated by the separate sterilization processes.
2. Description of Related Art
Monomer and polymer adhesives are used in both industrial (including household) and medical applications. Included among these adhesives are the 1,1-disubstituted ethylene monomers and polymers, such as the α-cyanoacrylates. Since the discovery of the adhesive properties of such monomers and polymers, they have found wide use due to the speed with which they cure, the strength of the resulting bond formed, and their relative ease of use. These characteristics have made the α-cyanoacrylate adhesives the primary choice for numerous applications such as bonding plastics, rubbers, glass, metals, wood, and, more recently, biological tissues.
It is known that monomeric forms of α-cyanoacrylates are extremely reactive, polymerizing rapidly in the presence of even minute amounts of an initiator, including moisture present in the air or on moist surfaces such as animal (including human) tissue. Monomers of α-cyanoacrylates are anionically polymerizable or free radical polymerizable, or polymerizable by zwitterions or ion pairs to form polymers. Once polymerization has been initiated, the cure rate can be very rapid.
Medical applications of 1,1-disubstituted ethylene adhesive compositions include use as an alternate or an adjunct to surgical sutures and/or staples in wound closure, as well as for covering and protecting surface wounds such as lacerations, abrasions, burns, stomatitis, sores, minor cuts and scrapes, and other wounds. When an adhesive is applied to surfaces to be joined, it is usually applied in its monomeric form, and the resultant polymerization gives rise to the desired adhesive bond.
When such adhesive compositions are desired to be used in the medical arts, it is often required, or at least preferred, that the adhesive composition be sterile. Likewise, it is often required, or at least preferred, that the applicators used to apply the adhesive composition, also be sterile. A variety of sterilization methods are generally used to sterilize monomeric and polymeric compositions as well as the packaging of such kits. These methods include chemical, physical, and irradiation methods. Examples of chemical methods include exposure to ethylene oxide or hydrogen peroxide vapor. Physical methods of sterilization may include, for example, sterilization by dry or moist heat. Gamma irradiation, electron beam (e-beam) irradiation, and microwave irradiation are some common examples of irradiation methods. Aseptic filling may also be used to provide sterile compositions.
U.S. Pat. No. 6,143,805 to Hickey et al. discloses a method for sterilizing a liquid adhesive composition, and in particular embodiments an α-cyanoacrylate adhesive composition, by e-beam irradiation while it is enclosed in a container. After the container containing the liquid adhesive composition is sterilized by e-beam radiation, the container may be further subjected to a second sterilization step or process. The patent also discloses that the container may be placed in a kit with other components that need to be sterilized, after which the entire kit may then be sterilized. In addition to e-beam irradiation, the entire kit may be sterilized by chemical, physical or other techniques such as microwave irradiation or γ-irradiation.
U.S. Pat. No. 6,248,800 discloses a method for sterilizing a polymerizable cyanoacrylate ester composition in a shipping element comprising multiple individual packages of cyanoacrylate compositions. A packaging element, such as an ampoule made of glass, polyalkylene based polymers, metal foils or polyolefins, is filled with a cyanoacrylate ester composition comprising a polymerizable cyanoacrylate ester. These filled packaging elements are then placed into a shipping element and exposed to a sufficient dosage of e-beam radiation maintained at an initial fluence of at least 2 μCurie/cm2 to sterilize both the packaging elements and the cyanoacrylate ester composition therein without gelling the composition. The average bulk density of the materials comprising all of the packaging elements is less than about 0.2 gm/cm3. In another embodiment, the patent discloses first exposing the empty ampoule to a gas stream comprising a sufficient amount of ethylene oxide to reduce the level of bioburden on the ampoule, before filling the ampoule with the cyanoacrylate adhesive.
U.S. Pat. No. 5,997,544 discloses a process for producing sterile-packed bone cement, comprising providing a first and a second container connected through a sealing device between the containers. The first container contains a polymer powder and the second contains a monomer. The containers are sterilized by introducing a sterilizing gas, such as ethylene oxide, into the containers via sterile filters attached to both containers.
U.S. Pat. No. 3,954,174 discloses a unitary two-compartment package for sterile surgical articles. The package comprises two separate and sealed containers that are joined to each other. The containers are defined by walls of sheet material permeable to a sterilizing agent. The disclosed package permits the packaging of surgical articles that may require diverse means of sterilization in a single package. For example, a germicidal liquid in one container may be sterilized by exposure to cobalt radiation, while surgical drapes or applications in the second container are sterilized via ethylene oxide gas. Once the individual packages have been sterilized, they are joined to form the described package. The reference discloses the package itself as well as the separate sterilization of diverse surgical articles.
Despite the increasing use of cyanoacrylate adhesives in medical and non-medical applications, the need exists for new and improved liquid and gel or gel-like adhesive compositions, and kits containing such compositions that enable their use in still further and varied applications. At the same time, however, as the formulations of the liquid and gel or gel-like adhesive compositions change to adapt to such further and varied applications, new sterilization techniques are required in order to provide the desired sterilization of the kit and all of its components.